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Inter-fastigial projections along the roof of the fourth ventricle

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Abstract

The fastigial nucleus (FN) is a bilateral cerebellar integrative center for saccadic and vestibular control associated with non-motor functions such as feeding and cardiovascular regulation. In a previous study, we identified a tract of myelinated axons embedded in the subventricular zone (SVZ) that is located between the ependymal cells that form the dorsal wall of the ventricle and the glia limitans at the roof of the fourth ventricle González-González (Sci Rep 2017, 7:40768). Here, we show that this tract of axons, named subventricular axons or SVa, contains projection neurons that bilaterally interconnect both FNs. The approach consisted of the use of a battery of fluorescent neuronal tracers, transgenic mouse lines, and immunohistofluorescence. Our observations show that the SVa belong to a wide network of GABAergic projection neurons mainly located in the medial and caudal region of the FN. The SVa should be considered a part of a continuum of the cerebellar white matter that follows an alternative pathway through the SVZ, a region closely associated with the physiology of the fourth ventricle. This finding adds to our understanding of the complex organization of the FN; however, the function of the interconnection remains to be elucidated.

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Abbreviations

BG:

Bergmann glia

Cb:

Cerebellum

CFS:

Cerebrospinal fluid

DC:

Dorsal cochlear nu

ECs:

Ependymal cells

ECL:

Ependymal cell layer

FG:

Fluro-gold

Fl:

Flocculus

FN:

Fastigial nucleus

FR:

Fluoro-ruby

GiA:

Gigantocellular nu

icp:

Inferior cerebellar peduncle

IntA:

Anterior interpositus

LVe:

Lateral vestibular nu

LPGi:

Lateral paragigantocellular nu

Med:

Medial (fastigial) nu

MVePc:

Medial vestibular nu (parvocellular)

MVeMC:

Medial vestibular nu (magnocellular)

nu:

Nucleus

Pc:

Purkinje cell

pcn:

Precentral fissure, cerebellum

PnC:

Pontine reticular nu

Pr:

Prepositus hypoglossal nu

py:

Pyramidal tract

P7:

Prefacial zone

SpVe:

Spinal vestibular nu

Sp5:

Spinal trigeminal tract

SuVe:

Superior vestibular nu

SVa:

Subventricular axons

SVCC:

Subventricular cellular cluster

Unc:

Uncinate fasciculus

VCP:

Ventral cochlear posterior nu

VeCb:

Vestibulocerebellar nu

VMC:

Ventromedial cord

X:

Cerebellar lobule ten

x:

X nu

I:

Cerebellar lobule one

4 V:

Fourth ventricle

7 N:

Facial nu

References

  • Akerboom J, Calderón NC, Tian L, Wabnig S, Prigge M, Tolö J et al (2013) Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics. Front Mol Neurosci 6:1–29

    Article  Google Scholar 

  • Alvarez-Morujo AJ, Toranzo D, Blazquez JL, Pelaez B, Sanchez A, Pastor FE et al (1992) The ependymal surface of the fourth ventricle of the rat: a combined scanning and transmission electron microscopic study. Histol Histopathol 7:259–266

    CAS  PubMed  Google Scholar 

  • Angaut P, Bowsher D (1970) Ascending projections of the medial cerebellar (fastigial) nucleus: an experimental study in the cat. Brain Res 24:49–68

    Article  CAS  PubMed  Google Scholar 

  • Batton RR, Jayaraman A, Ruggiero D, Carpenter MB (1977) Fastigial efferent projections in the monkey: an autoradiographic study. J Comp Neurol 174:281–305

    Article  PubMed  Google Scholar 

  • Becerra-González M, Varman Durairaj R, Ostos Valverde A, Gualda EJ, Loza-Alvarez P et al (2020) Response to hypoxic preconditioning of glial cells from the roof of the fourth ventricle. Neuroscience 439:211–229

    Article  PubMed  Google Scholar 

  • Beitz AJ, Chan-Palay V (1979) A Golgi analysis of neuronal organization in the medial cerebellar nucleus of the rat. Neuroscience 4:47–63

    Article  CAS  PubMed  Google Scholar 

  • Benagiano V, Rizzi A, Lorusso L, Flace P, Saccia M, Cagiano R et al (2018) The functional anatomy of the cerebrocerebellar circuit: a review and new concepts. J Comp Neurol 526:769–989

    Article  PubMed  Google Scholar 

  • Bentivoglio M, Kuypers HG (1982) Divergent axon collaterals from rat cerebellar nuclei to diencephalon, mesencephalon, medulla oblongata and cervical cord. A fluorescent double retrograde labeling study. Exp Brain Res 46:339–356

    Article  CAS  PubMed  Google Scholar 

  • Berry M, Ibrahim M, Carlile J, Ruge F, Duncan A, Butt AM (1995) Axon-glial relationships in the anterior medullary velum of the adult rat. J Neurocytol 24:965–983

    Article  CAS  PubMed  Google Scholar 

  • Berry M, Hunter AS, Duncan A, Lordan J, Kirvell S, Tsang WL et al (1998) Axon-glial relations during regeneration of axons in the adult rat anterior medullary velum. J Neurocytol 27:915–937

    Article  CAS  PubMed  Google Scholar 

  • Brain Info (1991) National Primate Research Center, University of Washington. http://www.braininfo.org. (Accessed Aug 2019)

  • Brocklehurst G (1969) The development of the human cerebrospinal fluid pathway with particular reference to the roof of the fourth ventricle. J Anat 105:467–475

    CAS  PubMed  PubMed Central  Google Scholar 

  • Büttner U, Fuchs AF, Markert-Schwab G, Buckmaster P (1991) Fastigial nucleus activity in the alert monkey during slow eye and head movements. J Neurophysiol 65:1360–1371

    Article  PubMed  Google Scholar 

  • Canto CB, Witter L, De Zeeuw CI (2016) Whole-cell properties of cerebellar nuclei neurons in vivo. PLoS ONE 11:1–19

    Article  Google Scholar 

  • Carpenter MB (1959) Lesions of the fastigial nuclei in the rhesus monkey. Am J Anat 104:1–33

    Article  CAS  PubMed  Google Scholar 

  • Catapano LA, Magavi SSP, Macklis JD (2002) Neuroanatomical tracing of neuronal projections with fluoro-gold. In: Sanberg PR, Sanchez-Ramos JR (eds) Methods mol biol neural stem cells methods and protocols. Humana Press Inc., Totowa

    Google Scholar 

  • Chaudhry FA, Reimer RJ, Bellocchio EE, Danbolt NC, Osen KK, Edwards RH et al (1998) The vesicular GABA transporter, VGAT, localizes to synaptic vesicles in sets of glycinergic as well as GABAergic neurons. J Neurosci 18:9733–9750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Falcão AM, Marques F, Novais A, Sousa N, Ja P, Sousa JC (2012) The path from the choroid plexus to the subventricular zone: go with the flow! Front Cell Neurosci 6:34

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K et al (2018) A cortico-cerebellar loop for motor planning. Nature 563:113–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glickstein M, Strata P, Voogd J (2009) Cerebellum: history. Neuroscience 162(3):549–559

    Article  CAS  PubMed  Google Scholar 

  • Golanov EV, Regnier-Golanov AS, Britz GW (2017) Integrity of cerebellar fastigial nucleus intrinsic neurons is critical for the global ischemic preconditioning. Brain Sci 7:10

    Article  Google Scholar 

  • González-González MA, Gómez-González GB, González-Becerra M, Martínez-Torres A (2017) Identification of novel cellular clusters define a specialized area in the cerebellar periventricular zone. Sci Rep 7:40768

    Article  PubMed  PubMed Central  Google Scholar 

  • Grosche J, Kettenmann H, Reichenbach A (2002) Bergmann glial cells form distinct morphological structures to interact with cerebellar neurons. J Neu Res 68:138–149

    Article  CAS  Google Scholar 

  • Grzanna R, Moliver ME (1979) The locus coeruleus in the rat: an immunohistochemical delineation. Neuroscience 5:21–40

    Article  Google Scholar 

  • Helmchen C, Straube A, Buttner U (1994) Saccade-related activity in the fastigial oculomotor region of the macaque monkey during spontaneous eye movements in light and darkness. Exp Brain Res 98:474–482

    Article  CAS  PubMed  Google Scholar 

  • Homma Y, Nonaka S, Matsuyama K, Mori S (1995) Fastigiofugal projection to the brainstem nuclei in the cat: an anterograde PHA-L tracing study. Neurosci Res 23:89–102

    Article  CAS  PubMed  Google Scholar 

  • Husson Z, Rousseau CV, Broll I, Zeilhofer HU, Dieudonné S (2014) Differential GABAergic and glycinergic inputs of inhibitory interneurons and Purkinje cells to principal cells of the cerebellar nuclei. J Neurosci 34:9418–9431

    Article  PubMed  PubMed Central  Google Scholar 

  • Ito M (2006) Cerebellar circuitry as a neuronal machine. Prog Neurobiol 78:272–303

    Article  PubMed  Google Scholar 

  • Ito M (2012) The Cerebellum: brain for an Implicit Self. Pearson Education Inc, New Jersey

    Google Scholar 

  • Katoh YY, Benedek G (2003) Cerebellar fastigial neurons send bifurcating axons to both the left and right superior colliculus in cats. Brain Res 25:246–249

    Article  Google Scholar 

  • Katz LC, Burkhalter A, Dreyer WJ (1984) Fluorescent latex microspheres as a retrograde neuronal marker for in vivo and in vitro studies of visual cortex. Nature 310:498–500

    Article  CAS  PubMed  Google Scholar 

  • Kheradmand A, Zee DS (2011) Cerebellum and ocular motor control. Front Neurol 1(2):53

    Google Scholar 

  • Köbbert C, Apps R, Bechmann I, Lanciego JL, Mey J, Thanos S (2000) Current concepts in neuroanatomical tracing. Prog Neurobiol 62:327–351

    Article  PubMed  Google Scholar 

  • Koziol LF, Budding D, Andreasen N, D’Arrigo S, Bulgheroni S, Imamizu H et al (2014) Consensus paper: The cerebellum’s role in movement and cognition. Cerebellum 13:151–177

    Article  PubMed  PubMed Central  Google Scholar 

  • Larsson M (2017) Pax2 is persistently expressed by GABAergic neurons throughout the adult rat dorsal horn. Neurosci Lett 638:96–101

    Article  CAS  PubMed  Google Scholar 

  • Louvi A, Alexandre P, Métin C, Wurst W, Wassef M (2003) The isthmic neuroepithelium is essential for cerebellar midline fusion. Development 130:5319–5330

    Article  CAS  PubMed  Google Scholar 

  • Maricich SM, Herrup K (1999) Pax-2 expression defines a subset of GABAergic interneurons and their precursors in the developing murine cerebellum. J Neurobiol 41:281–294

    Article  CAS  PubMed  Google Scholar 

  • Noda H, Sugita S, Ikeda Y (1990) Afferent and efferent connections of the oculomotor region of the fastigial nucleus in the macaque monkey. J Comp Neurol 302:330–348

    Article  CAS  PubMed  Google Scholar 

  • Nolte C, Matyash M, Pivneva T, Schipke CG, Ohlemeyer C, Hanisch UK, Kirchhoff F, Kettenmann H (2001) GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue. Glia 33:72–86

    Article  CAS  PubMed  Google Scholar 

  • Oberdick J, Sillitoe RV (2011) Cerebellar zones: history, development, and function. Cerebellum 10:301–306

    Article  PubMed  Google Scholar 

  • Omori O, Umetani T, Sugioka K (1997) Projections from the subdivisions of the fastigial nucleus to the vestibular complex and the prepositus hypoglossal nucleus in the albino rat: an anterograde tracing study using biocytin. Kobe J Med Sci 43(1):37–54

    CAS  PubMed  Google Scholar 

  • Pedroarena KM, Kamphausen S (2008) Glycinergic synaptic currents in the deep cerebellar nuclei. Neuropharmacology 54:784–795

    Article  CAS  PubMed  Google Scholar 

  • Porrero C, Rubio-Garrido P, Avendaño C, Clascá F (2010) Mapping of fluorescent protein-expressing neurons and axon pathways in adult and developing Thy1-eYFP-H transgenic mice. Brain Res 1345:59–72

    Article  CAS  PubMed  Google Scholar 

  • Preibisch S, Saalfeld S, Tomancak P (2009) Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics 25(11):1463–1465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rasmussen A (1933) Origin and course of the fasciculus uncinatus (Russell) in the cat, with observations on other fiber tracts arising from the cerebellar nuclei. J Comp Neurol 57:165–197

    Article  Google Scholar 

  • Reyes-Haro D, González-González MA, Pétriz A, Rosas-Arellano A, Kettenmann H, Miledi R et al (2013) γ-Aminobutyric acid-ρ expression in ependymal glial cells of the mouse cerebellum. J Neurosci Res 91:527–534

    Article  CAS  PubMed  Google Scholar 

  • Robinson FR, Straube A, Fuchs AF (1993) Role of the caudal fastigial nucleus in saccade generation. II. Effects of muscimol inactivation. J Neurophysiol 70:1741–1758

    Article  CAS  PubMed  Google Scholar 

  • Russell JSR, Horsley VAH (1895) XIV. Degenerations consequent on experimental lesions of the cerebellum. Phil Trans R Soc Lond B 186:633–660. https://doi.org/10.1098/rstb.1895.0014

    Article  Google Scholar 

  • Schmued LC, Heimer L (1990) Iontophoretic injection of fluoro-gold and other fluorescent tracers. J Histochem Cytochem 38:721–723

    Article  CAS  PubMed  Google Scholar 

  • Schofield BR (2008) Retrograde axonal tracing with fluorescent markers. Curr Protoc Neurosci 17:1–24. https://doi.org/10.1002/0471142301.ns0117s43

    Article  Google Scholar 

  • Siebold C, Glonti L, Glasauer S, Büttner U (1997) Rostral fastigial nucleus activity in the alert monkey during three-dimensional passive head movements. J Neurophysiol 77:1432–1446

    Article  CAS  PubMed  Google Scholar 

  • Uusisaari M, Knöpfel T (2008) GABAergic synaptic communication in the GABAergic and non-GABAergic cells in the deep cerebellar nuclei. Neuroscience 156:537–549. https://doi.org/10.1016/j.neuroscience.2008.07.060

    Article  CAS  PubMed  Google Scholar 

  • Uusisaari M, Knöpfel T (2012) Diversity of neuronal elements and circuitry in the cerebellar nuclei. Cerebellum 11:420–421

    Article  PubMed  Google Scholar 

  • Uusisaari M, Obata K, Knöpfel T (2007) Morphological and electrophysiological properties of GABAergic and non-GABAergic cells in the deep cerebellar nuclei. J Neurophysiol 97(1):901–911

    Article  CAS  PubMed  Google Scholar 

  • Vercelli A, Repici M, Garbossa D, Grimaldi A (2000) Recent techniques for tracing pathways in the central nervous system of developing and adult mammals. Brain Res Bull 51(1):11–28

    Article  CAS  PubMed  Google Scholar 

  • Voogd J (1964) The cerebellum of the cat: Structure and fiber connections. Thesis, Leiden. Assen: van Gorcum.

  • Voogd J (1967) Comparative aspects of the structure and fiber connexions of the mammalian cerebellum. In: Fox CA, Snider RS, Leiden S (eds) Progress in Brain Research: Cerebellum. Elsevier, The Netherlands

    Google Scholar 

  • Voogd J, Glickstein M (1998) The anatomy of the cerebellum. Trends Neurosci 21:370–375

    Article  CAS  PubMed  Google Scholar 

  • Voogd J, Jaarsma D, Marani E (1996) The Cerebellum chemoarchitecture and anatomy. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy. Elsevier, The Netherlands

    Google Scholar 

  • Voogd J, Shinoda Y, Ruigrok TJH, Sugihara I (2013) Cerebellar nuclei and the inferior olivary nuclei: organization and connections. In: Manto M, Schmahmann JD, Rossi F, Gruol DL, Koibuchi N (eds) Handbook of the cerebellum and cerebellar disorders. Springer, Dordrecht, pp 419–421

    Google Scholar 

  • Walberg F, Pompeiano O, Westrum LE, Hauglie-Hanssen E (1962) Fastigioreticular fibers in the cat. An experimental study with silver methods. J Comp Neurol 119:187–199

    Article  CAS  PubMed  Google Scholar 

  • Weisheit G, Gliem M, Endl E, Pfeffer PL, Busslinger M, Schilling K (2006) Postnatal development of the murine cerebellar cortex: formation and early dispersal of basket, stellate and Golgi neurons. Eur J Neurosci 24:466–478

    Article  PubMed  Google Scholar 

  • Xu FD, Zhang Z, Frazier DT (2001) Microinjection of acetazolamide into the fastigial nucleus augments respiratory output in the rat. J Appl Physiol 91:2342–2350

    Article  CAS  PubMed  Google Scholar 

  • Yamada J, Noda H (1987) Afferent and efferent connections of the oculomotor cerebellar vermis in the macaque monkey. J Comp Neurol 265:224–241

    Article  CAS  PubMed  Google Scholar 

  • Zhang XY, Wang JJ, Zhu JN (2016) Cerebellar fastigial nucleus: from anatomic construction to physiological functions. Cerebel Ataxias 3:9

    Article  Google Scholar 

  • Zhu JN, Yung WH, Kwok-Chong Chow B, Chan YS, Wang JJ (2006) The cerebellar hypothalamic circuits: potential pathways underlying cerebellar involvement in somatic-visceral integration. Brain Res Rev 52:93–106

    Article  PubMed  Google Scholar 

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Acknowledgements

This project was supported by grants from Consejo Nacional de Ciencia y Tecnología (CONACyT) (A1S7659) and Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT-DGAPA) (IN204520) to AMT. GBGG is a doctoral student from Programa de Doctorado en Ciencias Biomédicas, at Universidad Nacional Autónoma de México (UNAM), and was supported by CONACyT fellowship 277694. For the kindly donation of mice and materials, we thank Dr. Annalisa Buffo (NICO Institute-Italy), M. Condés-Lara and G. Rojas Piloni (Instituto de Neurobiología-INB, UNAM, Mexico), and H. Kettenmann (MDC-Berlin). We thank Dr. D. Escalante (IFC-UNAM) and R. Arellano (INB-UNAM) for suggestions and feedback. We thank the INB-Core Facilities for their technical support: unit of Microscopy (L. Palma-Tirado, E. N. Hernández-Ríos), and animal facility (A. Castilla-Leon, M. García-Servin, M.A. Carbajo). We also appreciate the technical backing of G. Martinez-Lorenzana, R. Olivares-Moreno and A.E. Espino Saldaña; the input and manuscript editing by M.A. González-González; and the English grammar editing by Dr. M. C. Jeziorski and J. G. Norris.

Funding

Funding provided to Consejo Nacional de Ciencia y Tecnología (MX): 277694; Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México: IN204520; Consejo Nacional de Ciencia y Tecnología (MX): A1S7659.

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GBGG conducted the experiments. AMT and GBGG designed the work, analyzed data, and wrote the paper.

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Correspondence to Ataúlfo Martínez-Torres.

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All experiments were designed to prevent animal suffering and discomfort at any moment. The animal protocol (INEU/SA/CB089) was approved by the Institutional Bioethics Committee of the Instituto de Neurobiología, Universidad Nacional Autónoma de México, in accordance with national (NOM-062-ZOO-1999) and international guidelines (National Institutes of Health, USA).

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Gómez-González, G.B., Martínez-Torres, A. Inter-fastigial projections along the roof of the fourth ventricle. Brain Struct Funct 226, 901–917 (2021). https://doi.org/10.1007/s00429-021-02217-8

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